The cyclic ketone 4-(3,4-dichlorophenyl)-3,4-dihydro-1-(2H)-naphthalenone (hereinafter referred to as "DCPN") is an important precursor in the formulation of an anti-depressant drug. See U.S. Pat. No. 4,536,518. Enantiomeric resolution of this precursor from racemic mixtures is currently limited to analytical scale chromatography. However, there is no known process for large scale, economical separation of DCPN.
The use of cyclodextrins for enantiomeric resolution of racemic mixtures of various optically active compounds is known. See, for example, Jin et al., 1 Chirality 137 (1989), which discloses the formation of cyclodextrin crystalline inclusion complexes of racemic 1-dimethylaminonaphthalene-5-sulfonyl [dansyl] amino acids in aqueous solutions of cyclodextrin, followed by precipitation of the complex by pH adjustment, and by selective recrystallization. However, such a process is suitable only for the separation of enantiomers, such as amino acids, that have water-ionizable acid groups that may be rendered insoluble by the protonation which occurs in an acidic pH range. Benschop et al., in Chemical Communications, pp 1431-1432 (1970), disclose the partial resolution of the liquid enantiomer isopropyl methyl phosphinate using beta-cyclodextrin complex formation as one of the steps in the resolution. The beta-cyclodextrin was suspended in the liquid phosphinate and a trace amount of water was added, causing the suspension to solidify into a crystalline mass. After 24 hours, the crystalline mass was washed with ether, with the ethereal phase containing the (+)-enantiomer 17% enriched in optical purity. Such a partial resolution has little practical value, however.
In general, no method has been devised in the art of enantiomeric resolution to predict those chiral moieties that may be resolved by complexation with cyclodextrins, let alone any specific methodology having universal application.